# Genetically Modified Gamma Delta T Cells to Target SIV Reservoirs

> **NIH NIH R33** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $494,712

## Abstract

Currently there is no cure available for HIV/AIDS. Although antiretroviral therapy (ART) is effective in
suppressing circulating HIV levels, it does not eliminate the latent and persistent viral reservoirs and the virus
rebounds following ART-interruption. Thus, curative therapies are urgently needed to clear the virus from
infected people and eliminate the dependence on lifelong ART. Recent clinical success of Chimeric antigen
receptor (CAR) T cells in leukemia and lymphoma have demonstrated that redirecting CTL activity of T cells
with specific CAR expression can overcome the limitations of autologous CTL functions. This project aims to
redirect the natural cytotoxicity of gamma delta (γδ) T cells against SHIV-infection using CD4-CARs that can
recognize infected cells by targeting HIV-Env. The CD4-CAR will be coupled with maC46 expression that will
prevent HIV fusion and thereby protect the CAR-γδ T cells from getting infected in vivo. Our data in rhesus
macaques show readily available γδ T cells in lymph nodes and bone marrow at levels similar to peripheral
blood, and are particularly enriched in gut mucosa, liver, spleen, and lungs, all potential reservoir tissues for
residual HIV infection during ART. Based on their unique functional properties, including (i) well-documented
CTL activity in immunotherapy of cancer, (ii) tissue migration, (iii) innate anti-HIV/SIV CTL/effector functions,
and (iv) continued stimulation through gut microbial ligands; we hypothesize that CAR-γδ T cells will serve
as potent anti-HIV CTLs resistant to HIV infection, and migrate to tissues independent of HIV-
stimulation to continually target viral reservoirs.
 In the R21 phase, we will determine the feasibility of autologous CAR-γδ T cell adoptive transfer for
migration and persistence in tissues and their in vivo response to SHIV infection in rhesus macaques. In vivo
(i) distribution, (ii) proliferation, (iii) persistence; and (iv) ex vivo CTL/cytokine effector functions will be
examined in the CD4-CAR-γδ T cell-treated animals and compared with the vector control group that receive
vector transduced autologous γδ T cells.
 In the R33 phase, we will determine the feasibility of CAR-γδ T cell immunotherapy for targeting viral
reservoirs in the clinical setting of SHIV-infected macaques on effective ART. The effects of the adoptively
transferred CAR-γδ T cells on viral load will be evaluated in lymphoid and mucosal tissue reservoirs. The
persistence and homing, CTL activity, selective expansion, and ultimately, the efficacy of adoptive transfer with
CD4-CAR-γδ T cells will be compared with vector control group.
 Since rhesus macaque is an important pre-clinical model for both HIV pathogenesis and gene therapy, the
evaluation of CAR-γδ T cell immunotherapy in rhesus/SHIV model has high translational value. The ability of
CAR-γδ T cells to control viremia following withdrawal of ART would be a significant advancement in HIV
treatment and would strongly promote a new ...

## Key facts

- **NIH application ID:** 10314034
- **Project number:** 5R33AI136100-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Namita Rout
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,712
- **Award type:** 5
- **Project period:** 2018-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314034

## Citation

> US National Institutes of Health, RePORTER application 10314034, Genetically Modified Gamma Delta T Cells to Target SIV Reservoirs (5R33AI136100-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314034. Licensed CC0.

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